Our definitive research goal is the development of a safe and efficacious recombinant subunit childhood vaccine for dengue virus to protect against hemorrhagic fever/dengue shock syndrome, a principal cause of hospitalization among children in Southeast Asia and a growing threat in the Americas. In our Phase I research, we established an animal cell system that expressed dengue proteins efficiently. The proteins appeared to possess a native-like conformation and induced virus-neutralizing antibodies in mice. In the mouse challenge model, they conferred significant protection against dengue virus. Our Phase II research will focus on novel methods of enhancing the immunogenicity of the Drosophila- expressed antigens to meet the stringent efficacy and dose requirements of a pediatric product. The effectiveness of these candidate vaccines will be evaluated in both the mouse and primate models of dengue infection. PROPOSED COMMERCIAL APPLICATION: Dengue virus, the agent of dengue fever, is gaining a worldwide distribution in the tropics and subtropics and is estimated to infect up to 100 million individuals per year. The proposed research will test the feasibility of expressing particle- forming recombinant dengue proteins in cultured Drosophila cells. These particles may be highly immunogenetic and suitable for a defined subunit vaccine.